Safety Study of Preimplantation Factor (PIF-1) to Treat Acute Steroid-Resistant Graft-Versus-Host Disease (GVHD)

Graft Vs Host Disease Clinical Trial

— PIF1GVHD  

Official title:

Phase I Clinical Trial to Assess Safety of Synthetic Preimplantation Factor (PIF-1) in Patients With Steroid-Resistant Acute Graft-Versus-Host Disease (GVHD) After Allogeneic Hematopoietic Stem-Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00517907
• Other study ID #: PIF1BMT-HMO-CTIL
• Status: Not yet recruiting
• Phase: Phase 1
• First received: August 16, 2007
• Last updated: June 10, 2015
• Start date: January 2016
• Est. completion date: January 2018

Study information

• Verified date: August 2008
• Source: Hadassah Medical Organization
• Contact: Reuven Or, MD
• Phone: +972-2-677-8357
• Email: reuvenor[@]hadassah.org.il
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

The primary goal of this study is to determine the safety and tolerability of a novel peptide - preimplantation factor (PIF-1) - in patients who develop acute steroid-resistant graft-versus-host disease (GVHD) after matched bone marrow transplant (BMT).

Following matched BMT, patients will be placed on standard GVHD preventive therapy (cyclosporine); those who do not respond to cyclosporine are placed on a high-dose steroid regimen for 3 days. Patients that do not respond to this standard treatment will be given PIF-1 subcutaneously for 14 days.

Clinical data and samples will be collected, during PIF-1 administration and for an additional three months thereafter, to examine the long-term effect of PIF-1 treatment on the patients' GVHD status.

Description:

Allogeneic BMT is a well-established treatment modality for malignant and non-malignant hematological diseases. Mature donor T cells within the stem-cell graft are the main mediators of the beneficial immune effects, but they are also responsible for the induction of GVHD, which becomes the major cause of morbidity and mortality post-transplant. Acute GVHD occurs within a 100-day period post-transplant and generally is manifested by dermatitis, enteritis, and hepatitis. The treatment of GVHD continues to be a challenge. To eliminate undesirable host-derived hematopoietic elements before BMT, patients are traditionally treated with myeloablative conditioning regimens involving high-dose chemotherapy and total-body irradiation. Standard GVHD prophylaxis and therapy comprise drugs that cause generalized immune suppression and place patients in danger of opportunistic infections and tumor relapse. For acute GVHD prevention, cyclosporine is often used; however, it is frequently necessary to administer long-term high-dose steroids as well.

An acute GVHD patient's lack of response to steroids is associated with poor prognosis. The ideal prophylaxis treatment for BMT patients would be one that prevented the graft from attacking the host, and that modulated the host's immune response so that it would accept the transplant, while maintaining its ability to protect the body against opportunistic hostile agents.

Pregnancy is an immune paradox: it allows maternal (host) acceptance of a semi-allograft (embryo), while it does not cause graft-versus-host or host-versus-graft reactions against the host/mother, or immune suppression. Therefore, the pregnant immunological status is compatible with the desired immune profile in patients undergoing BMT. By replicating the immune profile present in pregnancy in BMT patients, we may be able to reduce the occurrence of GVHD-related morbidity and mortality rates.

Preimplantation factor (PIF-1) is a novel, embryo-secreted peptide whose synthetic version matches the native peptide's properties. PIF-1 appears to play an important role in mediating the maternal response to pregnancy in mammals. In preclinical studies, PIF-1 has been found to be effective in preclinical BMT-GVHD models, without apparent toxicity.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 70 Years

Eligibility

Inclusion Criteria:

• Acute steroid-resistant GVHD post matched BMT

Exclusion Criteria:

• Morbidity unrelated to GVHD

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Vs Host Disease

Intervention

Drug:
• Preimplantation factor (PIF-1)
The study will include 6 patients and will last for at least six months. The first three patients will receive PIF-1 (0.5 mg/kg/day for 14 days) by subcutaneous injection. The dosage in the next three patients may be increased to 1 mg/kg/day for 14 days. Patients will be treated serially: each patient will be followed for 2 weeks after cessation of PIF-1 administration before the next patient begins PIF-1 administration.

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (2)

Lead Sponsor	Collaborator
Hadassah Medical Organization	BioIncept LLC

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of PIF-1 in steroid-resistant patients who develop acute GVHD, as evidenced by clinical and laboratory indices		within 90 days after first PIF-1 injection	Yes
Secondary	Therapeutic effect of PIF-1 on participants' acute GVHD status, as determined by comparison with the clinical and laboratory indices before intervention		within 90 days after first PIF-1 injection	No